Natural menopause typically occurs in women during middle age and is often described as an ovarian shutdown. Menopause is associated with a profound decrease in circulating levels of estrogens. Currently, there are a large variety of disorders and conditions that are attributed to the reduction of estrogen levels. These disorders and conditions include hot flashes, dryness and atrophy of the vagina, parathesia, dyspareunia, osteoporosis, female sexual dysfunction, and an increase in cardiovascular disease. In an effort to reduce these disorders and conditions, estrogens are administered to women in a so-called “estrogen replacement therapy”. Estrogen replacement therapy continues to be the primary treatment of such disorders and conditions associated with menopause.
Women, particularly perimenopausal, menopausal and postmenopausal women, often experience a wide variety of conditions and disorders attributable to estrogen deprivation. Estrogen deprivation is most often the result of loss of ovarian function. Providing dosages of estrogen is effective for the control or prevention of such conditions, particularly in controlling or preventing hot flashes and vaginal atrophy, along with retarding or preventing osteoporosis. Estrogen is typically administered alone or in combination with progestin.
As disclosed in U.S. Pat. No: Re. 36,247 to Plunkett et al., estrogen alone, given in small doses, on a continuous basis, is partially effective in patients for the control of the above symptoms and problems associated therewith. However, women who continuously take low-dose estrogen may risk developing endometrial hyperplasia, possibly leading to uterine carcinoma.
Approximately ten percent of women who are administered cyclic estrogen replacement therapy experience withdrawal bleeding between the cycles of the estrogens prescribed. To help reduce the development of endometrial hyperplasia, a progestin agent is often administered during the last 7-10 days of each estrogen cycle (of 28 to 30 days). When the progestin agent is administered cyclically, for example, during the last seven to ten days of the cycle, withdrawal bleeding regularly occurs. See, Whitehead, Am. J. Obs/Gyn., 142, 6, 791-795 (1982). When the progestin agent is administered continuously, random bleeding occurs, which is referred to as “breakthrough bleeding”.
There are numerous other estrogen/progestin regimens that have been suggested for treatment of menopausal symptoms. For example, U.S. Pat. No. 4,425,339, issued to Pitchford, discloses a method for treating menopausal symptoms including a four phase sequence of estrogen and progestogen administration. U.S. Pat. No. 5,043,331, issued to Hirvonen et al., discloses a lengthy three step process of estrogen and progestogens. U.S. Pat. No. 5,827,843, issued to Koninckx, discloses a preparation for substitution therapy and oral contraception wherein at least one progestogen and at least one estrogen is administered. U.S. Pat. No. 5,891,867, issued to Lanquetin et al., relates to a method of treating estrogen deficiencies in menopausal women using three different sequences of an estrogen followed by an estrogen progestogen combination and a placebo over the duration of a month. U.S. Pat. No. 5,108,995, issued to Casper et al., discloses a hormone preparation and method wherein the doses are arranged in alternating estrogen dominant phases and progestin dominant phases and each phase consists of from one to four consecutive daily unit doses. Finally, U.S. Pat. No. 5.208,225, issued to Boissonneault et al., discloses compositions that contain fixed combinations of a synthetic estrogen and a synthetic progestogenic agent. However, despite the administration of the above therapies there is room for improvement to treat vasomotor symptoms. Thus, it may be desirable to relieve vasomotor symptoms through alternative methods of estrogen therapy using a progestin agent.